Cancer cells need fat to spread

Andrew Quinn

Cancer cells need fat to help them spread around the bodies, a new study found.

The cells needs “roads” to travel around the body and use fat to build these.

But if scientists can switch off the cells ability to eat these fatty acids then they could stop cancers spreading.

Currently chemotherapy and radiotherapy can treat many cancers but the majority of deaths are caused when cancer spreads.

To spread cancer cells must find a pre-existing ‘road’ or build a new ‘road’ to travel on.

In a breakthrough scientists from The Flanders Institute for Biotechnology found the cells has increased need for fat to grow these ‘roads’ known as lymphatic vessels - a special kind of blood vessels.

Lymphatic vessels, a specialised kind of vessels transporting fluid rather than blood, are a primary route of cancer cell spread.

But the formation of new lymphatic vessels, termed lymphangiogenesis, is a poorly understood process, which currently lacks clinically approved drugs to prevent their growth during disease.

Lead author Professor Dr Peter Carmeliet and colleagues investigated the metabolism of nutrients by lymphatic vessels.

The study published in Nature began with a simple observation that lymphatics use more fat - fatty acids - compared to blood vessels.

By using drugs to prevent fat utilisation by lymphatics prevented lymphatic growth, an important step in translating this finding to the cancer setting and inhibition of metastasis.

In order to understand why these cells are so reliant on fat, the researchers investigated how lymphatics develop.

They ‘transform’ from blood vessels during embryonic development, and the signals that transform blood vessels to lymphatics also change their ‘taste’ to prefer eating fat.

The discovery found that this ‘transformation’ relies on an increase of fat utilisation.

The fat used to generate molecules which can modify important factors that regulate the expression of the genetic code, termed epigenetic changes, which can ensure the function of lymphatics.

The hard-wiring of the genetic code (DNA) itself is not altered by fat, but the utilisation of this code that defines the lymphatic gene signature is modulated.

But resupplying another fat nutrient source could restore the growth and function of lymphatics.

Dr Brian Wong said: “Our study shows that the usage of fat by lymphatics is programmed in their development, and required for their growth and function.

“We have demonstrated by enhancing or preventing the usage of fat (or fat byproducts), we can control the growth of lymphatics.”

The next steps to preventing cancer cell spread and treating cancer patients.

Future research will test fat usage inhibitors for their ability to reduce metastasis in different types of cancer.

It will also test whether dietary fat supplements, for instance in the form of ketone bodies, used by athletes) can heal faulty lymphatics.

This is a major complication in cancer patients undergoing surgical cancer removal, which leads to the debilitating swelling and dysfunction of the arms and legs, termed lymphedema, for which no drug is available.

Prof Carmeliet added: “Our immediate next studies are focusing on further translating these findings to the cancer setting.

“Previously, we could not develop drugs to target the growth of lymphatic vessels because we did not understand how they develop and function.

“Our work demonstrates the importance of their reliance on fat, and provides essential steps towards developing effective drugs to prevent excessive lymphatic growth in cancer, but also to treat incapacitating complications of lymphedema.”